This retrospective study adhered to the tenets of the Declaration of Helsinki and was approved by the Institutional Review Board and Ethics Committee of Yeungnam University Hospital and Asan Medical Center. An exemption was granted from the requirement for informed consent because the present study was retrospective research. All the methods were performed in accordance with relevant guidelines and regulations. Fifty-two eyes of 52 patients who were diagnosed with primary RRD at Yeungnam University Hospital and Asan Medical Center from March 2017 to December 2018, and underwent successful operation, including vitrectomy or scleral buckling, were included and analyzed. Retinal detachment occurring due to retinal holes, tears or dialysis was considered primary RRD, and tractional/exudative retinal detachments were excluded. We only included relatively acute, uncomplicated primary RRD that had a disease onset of less than 1 month and showed successful reattachment after the primary operation. Macular involvement in retinal detachment was defined as macula-off RRD, and this terminology is used throughout the manuscript.
For the comparison analysis, 42 eyes with CSC were also collected. Eyes showing subretinal fluid without any definite retinal break and focal/diffuse dye leakage on FA with choroidal hyperpermeability on indocyanine green angiography were defined as having CSC.
Highly myopic eyes over -6 diopters or the presence of concomitant retinal vascular diseases such as diabetic retinopathy, retinal vein or artery occlusion, Coats’ disease and familiar exudative vitreoretinopathy were considered exclusion criteria. Eyes presenting with retinal or choroidal vascular disease in the fellow eye were also excluded because the fellow eye was analyzed as a control group. We also excluded secondary macular morphological changes, including Irvine-Gass cystoid macular edema, epiretinal membrane, and macular holes, which can occur postoperatively and can influence OCTA segmentation. All patients were asked about their underlying systemic diseases, such as diabetes mellitus or hypertension, and underwent a comprehensive eye examination, including best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, color fundus photography, spectral domain optical coherence tomography (OCT) ), and UWF FA.
Surgical procedures were performed by experienced retinal surgeons (YHY and JL). Surgical decision-making and procedures were performed at the surgeons’ discretion. Operations were conducted in the operating room under general or retrobulbar anesthesia with aseptic preparation. Vitrectomy was performed with 25-gauge instruments (Constellation Vision System; Alcon Laboratories Inc., Fort Worth, TX, USA). All vitrectomies were performed as follows: core vitrectomy, induction of posterior vitreous detachment, relief of vitreoretinal traction around the retinal break, subretinal fluid drainage, endolaser photocoagulation, and tamponade with perfluoropropane gas or silicone oil. Scleral buckling was performed with a silicone sponge combined with cryotherapy around the retinal break.
Optical coherence tomography
Spectral domain OCT (Spectralis; Heidelberg Engineering, Heldelberg, Germany) was performed at every patient visit to evaluate the status of retinal attachment and ellipsoid zone integrity. In RRD eyes, ellipsoid zone (EZ) integrity was graded according to the relative length ratio of the disrupted EZ in the single horizontal scan through the fovea: Grade 0: Intact EZ; Grade 1: less than 25% disruption; Grade 3: 25–50% disruption; and Grade 4: more than 50% disruption. In CSC eyes, the highest subretinal fluid (SRF) height at the fovea was measured manually using embedded software, which was provided by the manufacturer. SRF height was defined as the vertical distance from the tip of the RPE layer to the outer border of the detached retina at the fovea.
Optical coherence tomography angiography
Twenty-six eyes with macula-off RRD and 42 eyes with CSC underwent OCTA. Data from healthy fellow eyes were obtained as a control. To avoid segmentation error, OCTA images were obtained after successful reattachment of RRD or complete SRF dry-up of CSC. A 3 × 3 mm area centered in the fovea was scanned with either AngioVue (Optovue Inc., Fremont, CA, USA) or AngioPlex (Zeiss Meditec Inc., Dublin, CA, USA). Both superficial capillary plexus (SCP) and deep capillary plexus (DCP) slab images were obtained to analyze the retinal capillaries. Inadequate quality of images of which signal strength index was below 50 in AngioVue or 6 in AngioPlex were excluded. The SCP was segmented with an inner boundary of 3 µm below the internal limiting membrane and an outer boundary of 15 µm below the inner plexiform layer (IPL). The DCP was segmented with an inner boundary of 15 µm below the IPL and an outer boundary of 70 µm below the IPL. In the case of incorrect segmentation, we manually adjusted the boundary between the specific layers.
Then, vascular flow density and foveal avascular zone (FAZ) area were calculated from both capillary plexuses to quantify foveal vascular status using a previously described method with ImageJ software16. Relative density (ratio to normal fellow eye) was used to calculate vascular flow density results because two different OCTA devices were used to measure vascular flow density in the present study.
In the preliminary study, only age had a significant correlation with the DCP vascular density of CSC among the variables, including duration of macular detachment, refractive errors, SRF height and anti-vascular endothelial growth factor (VEGF) use, which were previously reported to be related to choroidal changes in CSC17.18. Therefore, comparing the results of CSC and RRD, age-matched groups were selected (42 eyes with CSC and 26 eyes with macula-off RRD) and analyzed to minimize age-related confounding factors.
Ultra-widefield fluorescein angiography
UWF FA (Optos 200 MA/200Tx; Optos PLC, Dunfermline, Scotland, United Kingdom) was performed before the operation to evaluate retinal perfusion status in all 52 RRD eyes (100%). Angiographic abnormalities, including vascular tortuosity, venous dilation, diffuse paravascular leakage, peripheral nonperfusion, marginal leakage, capillary stasis, delayed arteriovenous transit time, focal nonperfusion and neovascularization elsewhere, were graded and analyzed by a retinal specialist (JL). After successful operation and reattachment of the retina, UWF FA was taken again in 46 eyes (88%). The angiographic abnormalities described above were graded again for comparison.
All statistical analyzes were performed using the Statistical Package for the Social Sciences (version 21.0; SPSS Inc., IBM Company, Chicago, IL, USA). Continuous variables are presented as the mean ± standard deviation. Comparisons between groups were evaluated using Student’s t-test, chi-square test, or Fisher’s exact test, as appropriate. In all analyzes, a value of p< 0.05 was considered statistically significant.
Part of this study was presented at the Meeting of the Club Jules Gonin, Dubrovnik, Croatia, September 2020.